The catecholamine (CA) hypothesis explains depression as a deficiency of norepinephrine (NE) at specific brain loci, and consistent with this, almost all available antidepressant drugs enhance brain NE activity. Yet available antidepressants are imperfect because of slow onset of actio and numerous unwanted effects. Tyrosine, the amino acid precursor of NE, has been shown to enhance NE activity in the brains of experimental animals, and preliminary data in humans suggest it may have potential as an antidepressant. Moreover, it is possible that plasma concentrations of tyrosine, or the ratio of the tyrosine concentration oto those of other large neutral amino acids with which it competes for uptake into the brain, may identify depressed patients who are most likely to respond to tyrosine therapy. It is also conceivalbethat increases in plasma concentration or the tyrosine ratio during tyrosine theraphy may correlate with clinical improvement. Finally, it could be hypothesized that individuals with low urinary excretio of MHPG (the major metabolite of NE), who may have a low level of brain NE turnover, might be more likely to respond to tyrosine theraphy. To test these clinical and biochemical hypotheses, and to contrast tyrosine to a standard antidepressant drug, we propose to administer tyrosine, imipramine, and placebo to 75 non-bipolar depressed oupatients in a parallel-group, double-blind protocol. Patients who fail to improve on placebo or imipramine therapy may subsequently be treated open-lable with tyrosine, providing a partial crossover feature. Important biochemical variables to be studied before and during treatment include plasma amino acid concentrations and urinary excretion of MHPG.